α-mangostin: A dietary antioxidant derived from the pericarp of Garcinia mangostana L. inhibits pancreatic tumor growth in xenograft mouse model

Bilal Hafeez, Ala Mustafa, Joseph W. Fischer, Ashok Singh, Weixiong Zhong, Mohammed Ozair Shekhani, Louise Meske, Thomas Havighurst, Kyungmann Kim, Ajit Kumar Verma

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Aims: Pancreatic cancer (PC) is the most aggressive malignant disease, ranking as the fourth most leading cause of cancer-related death among men and women in the United States. In this study, we provide evidence of chemotherapeutic effects of α-mangostin, a dietary antioxidant isolated from the pericarp of Garcinia mangostana L. against human PC. Results: The chemotherapeutic effect of α-mangostin was determined using four human PC cells (PL-45, PANC1, BxPC3, and ASPC1). α-Mangostin resulted in a significant inhibition of PC cells viability without having any effects on normal human pancreatic duct epithelial cells. α-Mangostin showed a dose-dependent increase of apoptosis in PC cells. Also, α-mangostin inhibited the expression levels of pNF-κB/p65Ser552, pStat3Ser727, and pStat3Tyr705. α-Mangostin inhibited DNA binding activity of nuclear factor kappa B (NF-κB) and signal transducer and activator 3 (Stat3). α-Mangostin inhibited the expression levels of matrix metallopeptidase 9 (MMP9), cyclin D1, and gp130; however, increased expression of tissue inhibitor of metalloproteinase 1 (TIMP1) was observed in PC cells. In addition, i.p. administration of α-mangostin (6?mg/kg body weight, 5 days a week) resulted in a significant inhibition of both primary (PL-45) and secondary (ASPC1) human PC cell-derived orthotopic and ectopic xenograft tumors in athymic nude mice. No sign of toxicity was observed in any of the mice administered with α-mangostin. α-Mangostin treatment inhibited the biomarkers of cell proliferation (Ki-67 and proliferating cell nuclear antigen [PCNA]) in the xenograft tumor tissues. Innovation: We present, for the first time, that dietary antioxidant α-mangostin inhibits the growth of PC cells in vitro and in vivo. Conclusion: These results suggest the potential therapeutic efficacy of α-mangostin against human PC. Antioxid.

Original languageEnglish (US)
Pages (from-to)682-699
Number of pages18
JournalAntioxidants and Redox Signaling
Volume21
Issue number5
DOIs
StatePublished - Aug 10 2014

Fingerprint

Garcinia mangostana
Garcinia
Heterografts
Tumors
Antioxidants
Pancreatic Neoplasms
Growth
Neoplasms
Nude Mice
mangostin
Tissue Inhibitor of Metalloproteinase-1
NF-kappa B
Pancreatic Ducts
Cyclin D1
Proliferating Cell Nuclear Antigen
Cell proliferation
Metalloproteases
Biomarkers
Transducers

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

α-mangostin : A dietary antioxidant derived from the pericarp of Garcinia mangostana L. inhibits pancreatic tumor growth in xenograft mouse model. / Hafeez, Bilal; Mustafa, Ala; Fischer, Joseph W.; Singh, Ashok; Zhong, Weixiong; Shekhani, Mohammed Ozair; Meske, Louise; Havighurst, Thomas; Kim, Kyungmann; Verma, Ajit Kumar.

In: Antioxidants and Redox Signaling, Vol. 21, No. 5, 10.08.2014, p. 682-699.

Research output: Contribution to journalArticle

Hafeez, Bilal ; Mustafa, Ala ; Fischer, Joseph W. ; Singh, Ashok ; Zhong, Weixiong ; Shekhani, Mohammed Ozair ; Meske, Louise ; Havighurst, Thomas ; Kim, Kyungmann ; Verma, Ajit Kumar. / α-mangostin : A dietary antioxidant derived from the pericarp of Garcinia mangostana L. inhibits pancreatic tumor growth in xenograft mouse model. In: Antioxidants and Redox Signaling. 2014 ; Vol. 21, No. 5. pp. 682-699.
@article{690ef20892a545d6b796a1596b97dbd0,
title = "α-mangostin: A dietary antioxidant derived from the pericarp of Garcinia mangostana L. inhibits pancreatic tumor growth in xenograft mouse model",
abstract = "Aims: Pancreatic cancer (PC) is the most aggressive malignant disease, ranking as the fourth most leading cause of cancer-related death among men and women in the United States. In this study, we provide evidence of chemotherapeutic effects of α-mangostin, a dietary antioxidant isolated from the pericarp of Garcinia mangostana L. against human PC. Results: The chemotherapeutic effect of α-mangostin was determined using four human PC cells (PL-45, PANC1, BxPC3, and ASPC1). α-Mangostin resulted in a significant inhibition of PC cells viability without having any effects on normal human pancreatic duct epithelial cells. α-Mangostin showed a dose-dependent increase of apoptosis in PC cells. Also, α-mangostin inhibited the expression levels of pNF-κB/p65Ser552, pStat3Ser727, and pStat3Tyr705. α-Mangostin inhibited DNA binding activity of nuclear factor kappa B (NF-κB) and signal transducer and activator 3 (Stat3). α-Mangostin inhibited the expression levels of matrix metallopeptidase 9 (MMP9), cyclin D1, and gp130; however, increased expression of tissue inhibitor of metalloproteinase 1 (TIMP1) was observed in PC cells. In addition, i.p. administration of α-mangostin (6?mg/kg body weight, 5 days a week) resulted in a significant inhibition of both primary (PL-45) and secondary (ASPC1) human PC cell-derived orthotopic and ectopic xenograft tumors in athymic nude mice. No sign of toxicity was observed in any of the mice administered with α-mangostin. α-Mangostin treatment inhibited the biomarkers of cell proliferation (Ki-67 and proliferating cell nuclear antigen [PCNA]) in the xenograft tumor tissues. Innovation: We present, for the first time, that dietary antioxidant α-mangostin inhibits the growth of PC cells in vitro and in vivo. Conclusion: These results suggest the potential therapeutic efficacy of α-mangostin against human PC. Antioxid.",
author = "Bilal Hafeez and Ala Mustafa and Fischer, {Joseph W.} and Ashok Singh and Weixiong Zhong and Shekhani, {Mohammed Ozair} and Louise Meske and Thomas Havighurst and Kyungmann Kim and Verma, {Ajit Kumar}",
year = "2014",
month = "8",
day = "10",
doi = "10.1089/ars.2013.5212",
language = "English (US)",
volume = "21",
pages = "682--699",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "5",

}

TY - JOUR

T1 - α-mangostin

T2 - A dietary antioxidant derived from the pericarp of Garcinia mangostana L. inhibits pancreatic tumor growth in xenograft mouse model

AU - Hafeez, Bilal

AU - Mustafa, Ala

AU - Fischer, Joseph W.

AU - Singh, Ashok

AU - Zhong, Weixiong

AU - Shekhani, Mohammed Ozair

AU - Meske, Louise

AU - Havighurst, Thomas

AU - Kim, Kyungmann

AU - Verma, Ajit Kumar

PY - 2014/8/10

Y1 - 2014/8/10

N2 - Aims: Pancreatic cancer (PC) is the most aggressive malignant disease, ranking as the fourth most leading cause of cancer-related death among men and women in the United States. In this study, we provide evidence of chemotherapeutic effects of α-mangostin, a dietary antioxidant isolated from the pericarp of Garcinia mangostana L. against human PC. Results: The chemotherapeutic effect of α-mangostin was determined using four human PC cells (PL-45, PANC1, BxPC3, and ASPC1). α-Mangostin resulted in a significant inhibition of PC cells viability without having any effects on normal human pancreatic duct epithelial cells. α-Mangostin showed a dose-dependent increase of apoptosis in PC cells. Also, α-mangostin inhibited the expression levels of pNF-κB/p65Ser552, pStat3Ser727, and pStat3Tyr705. α-Mangostin inhibited DNA binding activity of nuclear factor kappa B (NF-κB) and signal transducer and activator 3 (Stat3). α-Mangostin inhibited the expression levels of matrix metallopeptidase 9 (MMP9), cyclin D1, and gp130; however, increased expression of tissue inhibitor of metalloproteinase 1 (TIMP1) was observed in PC cells. In addition, i.p. administration of α-mangostin (6?mg/kg body weight, 5 days a week) resulted in a significant inhibition of both primary (PL-45) and secondary (ASPC1) human PC cell-derived orthotopic and ectopic xenograft tumors in athymic nude mice. No sign of toxicity was observed in any of the mice administered with α-mangostin. α-Mangostin treatment inhibited the biomarkers of cell proliferation (Ki-67 and proliferating cell nuclear antigen [PCNA]) in the xenograft tumor tissues. Innovation: We present, for the first time, that dietary antioxidant α-mangostin inhibits the growth of PC cells in vitro and in vivo. Conclusion: These results suggest the potential therapeutic efficacy of α-mangostin against human PC. Antioxid.

AB - Aims: Pancreatic cancer (PC) is the most aggressive malignant disease, ranking as the fourth most leading cause of cancer-related death among men and women in the United States. In this study, we provide evidence of chemotherapeutic effects of α-mangostin, a dietary antioxidant isolated from the pericarp of Garcinia mangostana L. against human PC. Results: The chemotherapeutic effect of α-mangostin was determined using four human PC cells (PL-45, PANC1, BxPC3, and ASPC1). α-Mangostin resulted in a significant inhibition of PC cells viability without having any effects on normal human pancreatic duct epithelial cells. α-Mangostin showed a dose-dependent increase of apoptosis in PC cells. Also, α-mangostin inhibited the expression levels of pNF-κB/p65Ser552, pStat3Ser727, and pStat3Tyr705. α-Mangostin inhibited DNA binding activity of nuclear factor kappa B (NF-κB) and signal transducer and activator 3 (Stat3). α-Mangostin inhibited the expression levels of matrix metallopeptidase 9 (MMP9), cyclin D1, and gp130; however, increased expression of tissue inhibitor of metalloproteinase 1 (TIMP1) was observed in PC cells. In addition, i.p. administration of α-mangostin (6?mg/kg body weight, 5 days a week) resulted in a significant inhibition of both primary (PL-45) and secondary (ASPC1) human PC cell-derived orthotopic and ectopic xenograft tumors in athymic nude mice. No sign of toxicity was observed in any of the mice administered with α-mangostin. α-Mangostin treatment inhibited the biomarkers of cell proliferation (Ki-67 and proliferating cell nuclear antigen [PCNA]) in the xenograft tumor tissues. Innovation: We present, for the first time, that dietary antioxidant α-mangostin inhibits the growth of PC cells in vitro and in vivo. Conclusion: These results suggest the potential therapeutic efficacy of α-mangostin against human PC. Antioxid.

UR - http://www.scopus.com/inward/record.url?scp=84904426935&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904426935&partnerID=8YFLogxK

U2 - 10.1089/ars.2013.5212

DO - 10.1089/ars.2013.5212

M3 - Article

C2 - 24295217

AN - SCOPUS:84904426935

VL - 21

SP - 682

EP - 699

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 5

ER -