Deoxypodophyllotoxin Exerts Anti-Cancer Effects on Colorectal Cancer Cells Through Induction of Apoptosis and Suppression of Tumorigenesis
(2019) In International Journal of Molecular Sciences 20(11). p.1-16- Abstract
Deoxypodophyllotoxin (DPT) is a cyclolignan compound that exerts anti-cancer effects against various types of cancers. DPT induces apoptosis and inhibits the growth of breast, brain, prostate, gastric, lung, and cervical tumors. In this study, we sought to determine the effect of DPT on cell proliferation, apoptosis, motility, and tumorigenesis of three colorectal cancer (CRC) cell lines: HT29, DLD1, and Caco2. DPT inhibited the proliferation of these cells. Specifically, the compound-induced mitotic arrest in CRC cells by destabilizing microtubules and activating the mitochondrial apoptotic pathway via regulation of B-cell lymphoma 2 (Bcl-2) family proteins (increasing Bcl-2 associated X (BAX) and decreasing B-cell lymphoma-extra-large... (More)
Deoxypodophyllotoxin (DPT) is a cyclolignan compound that exerts anti-cancer effects against various types of cancers. DPT induces apoptosis and inhibits the growth of breast, brain, prostate, gastric, lung, and cervical tumors. In this study, we sought to determine the effect of DPT on cell proliferation, apoptosis, motility, and tumorigenesis of three colorectal cancer (CRC) cell lines: HT29, DLD1, and Caco2. DPT inhibited the proliferation of these cells. Specifically, the compound-induced mitotic arrest in CRC cells by destabilizing microtubules and activating the mitochondrial apoptotic pathway via regulation of B-cell lymphoma 2 (Bcl-2) family proteins (increasing Bcl-2 associated X (BAX) and decreasing B-cell lymphoma-extra-large (Bcl-xL)) ultimately led to caspase-mediated apoptosis. In addition, DPT inhibited tumorigenesis in vitro, and in vivo skin xenograft experiments revealed that DPT significantly decreased tumor size and tumor weight. Taken together, our results suggest DPT to be a potent compound that is suitable for further exploration as a novel chemotherapeutic for human CRC.
(Less)
- author
- publishing date
- 2019-05-28
- type
- Contribution to journal
- publication status
- published
- keywords
- Animals, Antineoplastic Agents/pharmacology, Apoptosis/drug effects, Caco-2 Cells, Carcinogenesis/drug effects, Colorectal Neoplasms/drug therapy, Drugs, Chinese Herbal, HT29 Cells, Humans, Male, Mice, Mice, Inbred BALB C, Microtubules/drug effects, Podophyllotoxin/analogs & derivatives, Tubulin Modulators/pharmacology
- in
- International Journal of Molecular Sciences
- volume
- 20
- issue
- 11
- pages
- 1 - 16
- publisher
- MDPI AG
- external identifiers
-
- pmid:31141929
- scopus:85067308751
- ISSN
- 1422-0067
- DOI
- 10.3390/ijms20112612
- language
- English
- LU publication?
- no
- id
- 2b2dfba5-74fd-4566-8593-f47080a0c111
- date added to LUP
- 2022-08-25 14:36:02
- date last changed
- 2024-06-27 21:05:58
@article{2b2dfba5-74fd-4566-8593-f47080a0c111, abstract = {{<p>Deoxypodophyllotoxin (DPT) is a cyclolignan compound that exerts anti-cancer effects against various types of cancers. DPT induces apoptosis and inhibits the growth of breast, brain, prostate, gastric, lung, and cervical tumors. In this study, we sought to determine the effect of DPT on cell proliferation, apoptosis, motility, and tumorigenesis of three colorectal cancer (CRC) cell lines: HT29, DLD1, and Caco2. DPT inhibited the proliferation of these cells. Specifically, the compound-induced mitotic arrest in CRC cells by destabilizing microtubules and activating the mitochondrial apoptotic pathway via regulation of B-cell lymphoma 2 (Bcl-2) family proteins (increasing Bcl-2 associated X (BAX) and decreasing B-cell lymphoma-extra-large (Bcl-xL)) ultimately led to caspase-mediated apoptosis. In addition, DPT inhibited tumorigenesis in vitro, and in vivo skin xenograft experiments revealed that DPT significantly decreased tumor size and tumor weight. Taken together, our results suggest DPT to be a potent compound that is suitable for further exploration as a novel chemotherapeutic for human CRC.</p>}}, author = {{Gamage, Chathurika D B and Park, So-Yeon and Yang, Yi and Zhou, Rui and Taş, İsa and Bae, Woo Kyun and Kim, Kyung Keun and Shim, Jung-Hyun and Kim, Eunae and Yoon, Goo and Kim, Hangun}}, issn = {{1422-0067}}, keywords = {{Animals; Antineoplastic Agents/pharmacology; Apoptosis/drug effects; Caco-2 Cells; Carcinogenesis/drug effects; Colorectal Neoplasms/drug therapy; Drugs, Chinese Herbal; HT29 Cells; Humans; Male; Mice; Mice, Inbred BALB C; Microtubules/drug effects; Podophyllotoxin/analogs & derivatives; Tubulin Modulators/pharmacology}}, language = {{eng}}, month = {{05}}, number = {{11}}, pages = {{1--16}}, publisher = {{MDPI AG}}, series = {{International Journal of Molecular Sciences}}, title = {{Deoxypodophyllotoxin Exerts Anti-Cancer Effects on Colorectal Cancer Cells Through Induction of Apoptosis and Suppression of Tumorigenesis}}, url = {{http://dx.doi.org/10.3390/ijms20112612}}, doi = {{10.3390/ijms20112612}}, volume = {{20}}, year = {{2019}}, }