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Anthocyanins From the Fruit of Vitis coignetiae Pulliat Potentiate the Cisplatin Activity by Inhibiting PI3K/Akt Signaling Pathways in Human Gastric Cancer Cells.

Lu JN, Lee WS, Nagappan A, Chang SH, Choi YH, Kim HJ, Kim GS, Ryu CH, Shin SC, Jung JM, Hong SC - J Cancer Prev (2015)

Bottom Line: In this study, in order to seeking an approach to increase the anti-cancer effects of CDDP with natural products.We found that AIMs enhanced anticancer effects of CDDP, which activity was additive but not synergistic.This study suggests that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat enhanced anti-cancer effects of CDDP by inhibiting Akt activity activated by CDDP.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju.

ABSTRACT

Background: Cisplatin (cis-diaminedichloroplatinum, CDDP) is a widely used chemotherapeutic agent for the treatment of many cancers. However, initial resistance to CDDP is a serious problem in treating these cancers. Vitis coignetiae Pulliat (Meoru in Korea) have shown anti-nuclear factor kappa B and anti-epidermal growth factor receptor activities in cancer cells.

Methods: In this study, in order to seeking an approach to increase the anti-cancer effects of CDDP with natural products. Here, we investigated anthocyanins isolated from Vitis coignetiae Pulliat (anthocyanidins isolated from meoru, AIMs) can enhance anti-cancer effects of cisplatin (CDDP) in stomach cancer cells. The cell viability of SNU-1 and SNU-16 cells after treated with AIMs and CDDP were analyzed by MTT assay. The expressions of Akt and X-linked inhibitor of apoptosis protein (XIAP) proteins were examined by western blot in AIMs- and CDDP-treated cells.

Results: We found that AIMs enhanced anticancer effects of CDDP, which activity was additive but not synergistic. AIMs suppressed Akt activity of the cancer cells activated by CDDP. AIMs also suppressed in XIAP an anti-apoptotic protein.

Conclusions: This study suggests that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat enhanced anti-cancer effects of CDDP by inhibiting Akt activity activated by CDDP.

No MeSH data available.


Related in: MedlinePlus

Effects of anthocyanins isolated from Vitis coignetiae Pulliat (anthocyanidins isolated from meoru, AIMs) on cis-diaminedichloroplatinum (CDDP)-induced apoptosis by regulating p-Akt in SNU-16 cells. SNU-16 cells were seeded at the density of 5 × 104 cells/mL. The cells were treated with CDDP (12 μg/mL) and/or AIMs (200 μM) for 24 hours. (A) Cell proliferation was assessed by MTT assay. The data are shown as mean ± SD of three independent experiments. aP < 0.05 versus the untreated group. bP < 0.05 versus the CDDP-treated group. (B) Equal amounts of cell lysate (30 μg) were resolved by SDS polyacrylamide gels and transferred onto nitrocellulose membranes. The membranes were probed with the indicated antibodies and detected by the enhanced chemiluminescence detection system. The results are from a representative experiment of at least three independent experiments that showed similar patterns. XIAP, X-linked inhibitor of apoptosis protein; PARP, poly adenosine diphosphate-ribose polymerase.
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f3-jcp-20-50: Effects of anthocyanins isolated from Vitis coignetiae Pulliat (anthocyanidins isolated from meoru, AIMs) on cis-diaminedichloroplatinum (CDDP)-induced apoptosis by regulating p-Akt in SNU-16 cells. SNU-16 cells were seeded at the density of 5 × 104 cells/mL. The cells were treated with CDDP (12 μg/mL) and/or AIMs (200 μM) for 24 hours. (A) Cell proliferation was assessed by MTT assay. The data are shown as mean ± SD of three independent experiments. aP < 0.05 versus the untreated group. bP < 0.05 versus the CDDP-treated group. (B) Equal amounts of cell lysate (30 μg) were resolved by SDS polyacrylamide gels and transferred onto nitrocellulose membranes. The membranes were probed with the indicated antibodies and detected by the enhanced chemiluminescence detection system. The results are from a representative experiment of at least three independent experiments that showed similar patterns. XIAP, X-linked inhibitor of apoptosis protein; PARP, poly adenosine diphosphate-ribose polymerase.

Mentions: Previously we reported that AIMs can induce apoptosis by reducing Bcl-2, XIAP through the inhibition of Akt-phosphorylation.14 To determine that AIMs enhance CDDP-induced apoptosis, we performed cell viability assay. As shown in Figure 3A, AIMs enhanced cytotoxicity of CDDP. To confirm this finding at the molecular level, we performed western blot analysis for apoptosis related factors and p-Akt. The suppression of Akt phosphorylation led to inhibition of XIAP and activation of apoptosis related enzyme (PARP and caspase 3). We found that AIMs enhance the cytotoxicity of CDDP by suppressing XIAP and Akt. This result suggests that AIMs can enhance the sensitivity of CDDP in p-53 mutant SNU-16 cells which is resistant to CDDP.


Anthocyanins From the Fruit of Vitis coignetiae Pulliat Potentiate the Cisplatin Activity by Inhibiting PI3K/Akt Signaling Pathways in Human Gastric Cancer Cells.

Lu JN, Lee WS, Nagappan A, Chang SH, Choi YH, Kim HJ, Kim GS, Ryu CH, Shin SC, Jung JM, Hong SC - J Cancer Prev (2015)

Effects of anthocyanins isolated from Vitis coignetiae Pulliat (anthocyanidins isolated from meoru, AIMs) on cis-diaminedichloroplatinum (CDDP)-induced apoptosis by regulating p-Akt in SNU-16 cells. SNU-16 cells were seeded at the density of 5 × 104 cells/mL. The cells were treated with CDDP (12 μg/mL) and/or AIMs (200 μM) for 24 hours. (A) Cell proliferation was assessed by MTT assay. The data are shown as mean ± SD of three independent experiments. aP < 0.05 versus the untreated group. bP < 0.05 versus the CDDP-treated group. (B) Equal amounts of cell lysate (30 μg) were resolved by SDS polyacrylamide gels and transferred onto nitrocellulose membranes. The membranes were probed with the indicated antibodies and detected by the enhanced chemiluminescence detection system. The results are from a representative experiment of at least three independent experiments that showed similar patterns. XIAP, X-linked inhibitor of apoptosis protein; PARP, poly adenosine diphosphate-ribose polymerase.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384714&req=5

f3-jcp-20-50: Effects of anthocyanins isolated from Vitis coignetiae Pulliat (anthocyanidins isolated from meoru, AIMs) on cis-diaminedichloroplatinum (CDDP)-induced apoptosis by regulating p-Akt in SNU-16 cells. SNU-16 cells were seeded at the density of 5 × 104 cells/mL. The cells were treated with CDDP (12 μg/mL) and/or AIMs (200 μM) for 24 hours. (A) Cell proliferation was assessed by MTT assay. The data are shown as mean ± SD of three independent experiments. aP < 0.05 versus the untreated group. bP < 0.05 versus the CDDP-treated group. (B) Equal amounts of cell lysate (30 μg) were resolved by SDS polyacrylamide gels and transferred onto nitrocellulose membranes. The membranes were probed with the indicated antibodies and detected by the enhanced chemiluminescence detection system. The results are from a representative experiment of at least three independent experiments that showed similar patterns. XIAP, X-linked inhibitor of apoptosis protein; PARP, poly adenosine diphosphate-ribose polymerase.
Mentions: Previously we reported that AIMs can induce apoptosis by reducing Bcl-2, XIAP through the inhibition of Akt-phosphorylation.14 To determine that AIMs enhance CDDP-induced apoptosis, we performed cell viability assay. As shown in Figure 3A, AIMs enhanced cytotoxicity of CDDP. To confirm this finding at the molecular level, we performed western blot analysis for apoptosis related factors and p-Akt. The suppression of Akt phosphorylation led to inhibition of XIAP and activation of apoptosis related enzyme (PARP and caspase 3). We found that AIMs enhance the cytotoxicity of CDDP by suppressing XIAP and Akt. This result suggests that AIMs can enhance the sensitivity of CDDP in p-53 mutant SNU-16 cells which is resistant to CDDP.

Bottom Line: In this study, in order to seeking an approach to increase the anti-cancer effects of CDDP with natural products.We found that AIMs enhanced anticancer effects of CDDP, which activity was additive but not synergistic.This study suggests that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat enhanced anti-cancer effects of CDDP by inhibiting Akt activity activated by CDDP.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju.

ABSTRACT

Background: Cisplatin (cis-diaminedichloroplatinum, CDDP) is a widely used chemotherapeutic agent for the treatment of many cancers. However, initial resistance to CDDP is a serious problem in treating these cancers. Vitis coignetiae Pulliat (Meoru in Korea) have shown anti-nuclear factor kappa B and anti-epidermal growth factor receptor activities in cancer cells.

Methods: In this study, in order to seeking an approach to increase the anti-cancer effects of CDDP with natural products. Here, we investigated anthocyanins isolated from Vitis coignetiae Pulliat (anthocyanidins isolated from meoru, AIMs) can enhance anti-cancer effects of cisplatin (CDDP) in stomach cancer cells. The cell viability of SNU-1 and SNU-16 cells after treated with AIMs and CDDP were analyzed by MTT assay. The expressions of Akt and X-linked inhibitor of apoptosis protein (XIAP) proteins were examined by western blot in AIMs- and CDDP-treated cells.

Results: We found that AIMs enhanced anticancer effects of CDDP, which activity was additive but not synergistic. AIMs suppressed Akt activity of the cancer cells activated by CDDP. AIMs also suppressed in XIAP an anti-apoptotic protein.

Conclusions: This study suggests that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat enhanced anti-cancer effects of CDDP by inhibiting Akt activity activated by CDDP.

No MeSH data available.


Related in: MedlinePlus