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Pachymic acid induces apoptosis via activating ROS-dependent JNK and ER stress pathways in lung cancer cells.

Ma J, Liu J, Lu C, Cai D - Cancer Cell Int. (2015)

Bottom Line: The in vivo efficacy of PA was measured using a NCI-H23 xenograft model in nude mice.Moreover, blockage of ROS production reversed PA-induced JNK and ER stress activation.Finally, PA inhibited the growth of NCI-H23 xenograft tumors without causing any host toxicity, and inhibited cell proliferation and induction of apoptosis of tumor cells in tumor xenograft tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032 China.

ABSTRACT

Background: Pachymic acid (PA), a lanostane-type triterpenoid from Poria cocos, has been reported to possess anti-emetic, anti-inflammatory, and anti-cancer properties. Nonetheless, the anti-tumor effect of PA in lung cancer cells remains unclear. Herein, we report the chemotherapeutic effects and underlying mechanisms of PA against human lung cancer.

Methods: The anti-proliferative ability of PA on lung cancer cells was assessed by MTT, colony formation and EdU proliferation assays. Flow cytometric analysis was used to detect cell cycle changes. Apoptosis was determined by annexin V/PI double-staining and the DNA ladder formation assays. The expressions of the apoptosis-related proteins were analysed by western blot. The in vivo efficacy of PA was measured using a NCI-H23 xenograft model in nude mice.

Results: PA exhibited anti-tumor effects in vitro accompanied by induction of G2/M phase arrest and apoptosis in NCI-H23 and NCI-H460 lung cancer cells. Mechanistically, our data showed that PA induced reactive oxygen species (ROS) production, resulting in the activation of both c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER) stress apoptotic pathways in lung cancer cells. Moreover, blockage of ROS production reversed PA-induced JNK and ER stress activation. Finally, PA inhibited the growth of NCI-H23 xenograft tumors without causing any host toxicity, and inhibited cell proliferation and induction of apoptosis of tumor cells in tumor xenograft tissues.

Conclusions: In summary, our study demonstrates that PA induces apoptosis through activation of the JNK and ER stress pathways in human lung cancer cells. Our findings provide a rationale for the potential application of PA in lung cancer therapy.

No MeSH data available.


Related in: MedlinePlus

PA inhibits tumor xenograft growth in vivo. a Anti-tumor activity of PA in nude mice bearing NCI-H23 tumors. Vehicle control and PA (10, 30 and 60 mg/kg) were administered for 3 weeks (5 days/week) by ip injection. Tumor volume was monitored. b Body weight of the mice. c H&E staining of the paraffin-embedded sections of various tissues (lung, liver, kidney and spleen) obtained from mice were performed to assess whether there were any abnormalities caused by the treatment. Scale bars are 100 μm. Data in the graphs represent the mean ± SD (n = 6). **p < 0.01 versus vehicle control.
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Fig4: PA inhibits tumor xenograft growth in vivo. a Anti-tumor activity of PA in nude mice bearing NCI-H23 tumors. Vehicle control and PA (10, 30 and 60 mg/kg) were administered for 3 weeks (5 days/week) by ip injection. Tumor volume was monitored. b Body weight of the mice. c H&E staining of the paraffin-embedded sections of various tissues (lung, liver, kidney and spleen) obtained from mice were performed to assess whether there were any abnormalities caused by the treatment. Scale bars are 100 μm. Data in the graphs represent the mean ± SD (n = 6). **p < 0.01 versus vehicle control.

Mentions: To evaluate the anti-tumor activity of PA in vivo, we used human lung cancer NCI-H23 tumor xenograft models. As seen in Fig. 4a, PA significantly suppressed tumor growth at doses of 30 and 60 mg/kg for 21 days compared with the control group. In addition, there is no significant difference in body weight change among the vehicle group and PA-treated groups (Fig. 4b). Moreover, there were no significant differences in the histological findings among the treatment and control groups in any of the other tissues examined (lung, liver, kidney and spleen) (Fig. 4c). These data showed that PA exhibited potent anti-tumor activity and high safety in vivo.Fig. 4


Pachymic acid induces apoptosis via activating ROS-dependent JNK and ER stress pathways in lung cancer cells.

Ma J, Liu J, Lu C, Cai D - Cancer Cell Int. (2015)

PA inhibits tumor xenograft growth in vivo. a Anti-tumor activity of PA in nude mice bearing NCI-H23 tumors. Vehicle control and PA (10, 30 and 60 mg/kg) were administered for 3 weeks (5 days/week) by ip injection. Tumor volume was monitored. b Body weight of the mice. c H&E staining of the paraffin-embedded sections of various tissues (lung, liver, kidney and spleen) obtained from mice were performed to assess whether there were any abnormalities caused by the treatment. Scale bars are 100 μm. Data in the graphs represent the mean ± SD (n = 6). **p < 0.01 versus vehicle control.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4524283&req=5

Fig4: PA inhibits tumor xenograft growth in vivo. a Anti-tumor activity of PA in nude mice bearing NCI-H23 tumors. Vehicle control and PA (10, 30 and 60 mg/kg) were administered for 3 weeks (5 days/week) by ip injection. Tumor volume was monitored. b Body weight of the mice. c H&E staining of the paraffin-embedded sections of various tissues (lung, liver, kidney and spleen) obtained from mice were performed to assess whether there were any abnormalities caused by the treatment. Scale bars are 100 μm. Data in the graphs represent the mean ± SD (n = 6). **p < 0.01 versus vehicle control.
Mentions: To evaluate the anti-tumor activity of PA in vivo, we used human lung cancer NCI-H23 tumor xenograft models. As seen in Fig. 4a, PA significantly suppressed tumor growth at doses of 30 and 60 mg/kg for 21 days compared with the control group. In addition, there is no significant difference in body weight change among the vehicle group and PA-treated groups (Fig. 4b). Moreover, there were no significant differences in the histological findings among the treatment and control groups in any of the other tissues examined (lung, liver, kidney and spleen) (Fig. 4c). These data showed that PA exhibited potent anti-tumor activity and high safety in vivo.Fig. 4

Bottom Line: The in vivo efficacy of PA was measured using a NCI-H23 xenograft model in nude mice.Moreover, blockage of ROS production reversed PA-induced JNK and ER stress activation.Finally, PA inhibited the growth of NCI-H23 xenograft tumors without causing any host toxicity, and inhibited cell proliferation and induction of apoptosis of tumor cells in tumor xenograft tissues.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032 China.

ABSTRACT

Background: Pachymic acid (PA), a lanostane-type triterpenoid from Poria cocos, has been reported to possess anti-emetic, anti-inflammatory, and anti-cancer properties. Nonetheless, the anti-tumor effect of PA in lung cancer cells remains unclear. Herein, we report the chemotherapeutic effects and underlying mechanisms of PA against human lung cancer.

Methods: The anti-proliferative ability of PA on lung cancer cells was assessed by MTT, colony formation and EdU proliferation assays. Flow cytometric analysis was used to detect cell cycle changes. Apoptosis was determined by annexin V/PI double-staining and the DNA ladder formation assays. The expressions of the apoptosis-related proteins were analysed by western blot. The in vivo efficacy of PA was measured using a NCI-H23 xenograft model in nude mice.

Results: PA exhibited anti-tumor effects in vitro accompanied by induction of G2/M phase arrest and apoptosis in NCI-H23 and NCI-H460 lung cancer cells. Mechanistically, our data showed that PA induced reactive oxygen species (ROS) production, resulting in the activation of both c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER) stress apoptotic pathways in lung cancer cells. Moreover, blockage of ROS production reversed PA-induced JNK and ER stress activation. Finally, PA inhibited the growth of NCI-H23 xenograft tumors without causing any host toxicity, and inhibited cell proliferation and induction of apoptosis of tumor cells in tumor xenograft tissues.

Conclusions: In summary, our study demonstrates that PA induces apoptosis through activation of the JNK and ER stress pathways in human lung cancer cells. Our findings provide a rationale for the potential application of PA in lung cancer therapy.

No MeSH data available.


Related in: MedlinePlus