The Flavonoid Apigenin Potentiates the Growth Inhibitory Effects of Gemcitabine and Abrogates Gemcitabine Resistance in Human Pancreatic Cancer Cells

Strouch, Matthew J.; Milam, Benjamin M.; Melstrom, Laleh G.; McGill, J. J.; Salabat, Mohammad R.; Ujiki, Michael; Ding, Xian; Bentrem, David J.

doi:10.1097/mpa.0b013e318193a074

Cited by 42 publications

(29 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[38][39][40][41][42] Some studies showed that apigenin, when used together with agents other than 5-FU, had greater apoptotic effects than when it was used alone. 43,44 Although many flavonoid members with apoptotic effects on the HT29 cell line have been studied, [45][46][47][48][49] the number of those tackling apigenin administration to HT29 cells remains limited. [48][49][50][51][52][53][54][55] Four of these studies evaluated the effect of apigenin on cell viability.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Effects of the Flavonoid Apigenin on Apoptotic Pathway Gene Expression on the Colon Cancer Cell Line (HT29)

Turktekin

Konac

Onen

et al. 2011

Journal of Medicinal Food

View full text Add to dashboard Cite

Apigenin (4',5,7-trihydroxyflavone) is one of the leading components supporting targeted treatment options. We explored the cytotoxic and apoptotic effects of various doses of apigenin administered alone and together with 5-fluorouracil (5-FU)-a chemotherapeutic agent with high cytotoxicity-for different incubation periods, on morphologic, DNA, RNA (messenger RNA [mRNA]), and protein levels on the p53 mutant HT29 human colon adenocarcinoma cell line. Treatment with apigenin alone for a 72-hour incubation at 90-μM dose resulted in an apoptotic percentage of 24.92% (P=.001). A higher percentage (29.13%) was observed after treatment with the same dose of apigenin plus 5-FU for the same incubation period (P=.001). These results were confirmed as mRNA and protein expression levels of caspase-3 increased 2.567-fold and mRNA expression levels of caspase-8 increased 3.689-fold compared with the control group. On the other hand, mRNA expression levels of mammalian target of rapamycin (mTOR) and cyclin D1 (CCND1) decreased by 0.423-fold and 0.231-fold, respectively. To our knowledge this is the first study showing that treatment with apigenin alone results in cell cycle arrest through activation of caspase cascade and stimulation of apoptosis in HT29 cells. It also shows that use of apigenin plus 5-FU further increases this effect. This study draws attention to the probable clinical effectiveness of apigenin plus a chemotherapeutic agent with high cytotoxicity. It also highlights the induction of desirable apoptotic effects by targeting the caspase cascade pathway through administration of reduced doses for shorter incubation periods.

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluation of the Effects of the Flavonoid Apigenin on Apoptotic Pathway Gene Expression on the Colon Cancer Cell Line (HT29)

Turktekin

Konac

Onen

et al. 2011

Journal of Medicinal Food

View full text Add to dashboard Cite

show abstract

“…The EC 50 of gemcitabine on MCF-7 cells was found to be 35mM at 24h treatment. Various studies have also shown its cytotoxicity towards various cancer cells (Pacini et al, 1999;Strouch et al, 2009;Hastak et al, 2010). However, it was found to have cytotoxic effects against normal cells also (Sharma et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Sulforaphane Inhibits Growth of Human Breast Cancer Cells and Augments the Therapeutic Index of the Chemotherapeutic Drug, Gemcitabine

Hussain¹,

Mohsin²,

Prabhu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Phytochemicals are among the natural chemopreventive agents with most potential for delaying, blocking or reversing the initiation and promotional events of carcinogenesis. They therefore offer cancer treatment strategies to reduce cancer related death. One such promising chemopreventive agent which has attracted considerable attention is sulforaphane (SFN), which exhibits anti-cancer, anti-diabetic, and anti-microbial properties. The present study was undertaken to assess effect of SFN alone and in combination with a chemotherapeutic agent, gemcitabine, on the proliferative potential of MCF-7 cells by cell viability assay and authenticated the results by nuclear morphological examination.

show abstract

“…Apigenin has additionally been reported to induce apoptosis of prostate and colon cancer cells through induction of death receptor 5, and to act synergistically with exogenous tumor necrosis factor-related apoptosis-inducing ligand to induce cell apoptosis (12). Furthermore, apigenin enhances the anticancer activity or minimizes the resistance of cancer cells to a number chemotherapeutics, including gemcitabine, paclitaxel, 5-fluorouracil and doxorubicin by inducing apoptosis (13)(14)(15)(16)(17). It was reported that apigenin sensitizes neuroblastoma cells to the anticancer drug etoposide by retention of p53 in cell nuclei (18).…”

Section: Introductionmentioning

confidence: 99%

Apigenin enhances the cisplatin cytotoxic effect through p53-modulated apoptosis

Liu

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. Epidemiological and experimental evidence suggests that dietary flavonoids, including apigenin, have anticancer roles. Apigenin has been reported to elevate p53, a critical molecule in the induction of apoptosis. The present study aimed to investigate whether apigenin, a dietary flavonoid, improves the cytotoxic effect of cisplatin in a cancer cell culture system, and to elucidate the mechanism of this effect. Multiple tumor cell types were treated with apigenin, cisplatin or both drugs. Cell viability was evaluated, and the cytotoxic effect was determined biochemically and microscopically. Treatment with apigenin increased cisplatin-induced DNA damage and the apoptosis of tumor cells in a p53-dependent manner. Apigenin, when used with cisplatin, inhibited cell proliferation and promoted mitogen-activated protein kinase activation and subsequent p53 phosphorylation, leading to p53 accumulation and upregulation of proapoptotic proteins. Cisplatin is one of the most commonly used chemotherapeutic drugs for malignant tumors, but resistance to this drug occurs. The current results therefore demonstrate that dietary flavonoids may diminish the resistance of cancers to cisplatin.

show abstract

The Flavonoid Apigenin Potentiates the Growth Inhibitory Effects of Gemcitabine and Abrogates Gemcitabine Resistance in Human Pancreatic Cancer Cells

Abstract: Combination treatment with apigenin and gemcitabine inhibited pancreatic cancer cell growth via cell cycle arrest, down-regulation of the prosurvival factor pAkt, and induction of apoptosis. Combination therapy may prove useful for the treatment of pancreatic cancer.

Cited by 42 publications

References 33 publications

Evaluation of the Effects of the Flavonoid Apigenin on Apoptotic Pathway Gene Expression on the Colon Cancer Cell Line (HT29)

Evaluation of the Effects of the Flavonoid Apigenin on Apoptotic Pathway Gene Expression on the Colon Cancer Cell Line (HT29)

Sulforaphane Inhibits Growth of Human Breast Cancer Cells and Augments the Therapeutic Index of the Chemotherapeutic Drug, Gemcitabine

Apigenin enhances the cisplatin cytotoxic effect through p53-modulated apoptosis

Contact Info

Product

Resources

About