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Tumor Discovery PPAR agonist and cancer

affecting other pathways related to cell migration, without of ranpirnase and rosiglitazone appears promising, as
increasing the expression of the surface proteins of these illustrated in Figure 2. The combination of rosiglitazone
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two receptors. 65 and all-trans-retinoic acid lowers the expression of
COX-2, matrix metallopeptidase 7 (MMP-7), and tissue
4.2. PPAR agonists for antiproliferative and inhibitor of metalloproteinase 1, induces cell cycle
apoptotic effects arrest at the G1 phase and consequently inhibits cell

Apoptosis, the body’s natural cell death process, is a proliferation in the human colorectal cancer cell line HCT-
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key area of focus in anticancer treatment. In cancer, the 15. In hepatocellular carcinoma (HCC) cells treated
suppression of the apoptotic pathway often occurs through with 5-fluorouracil, rosiglitazone activates the PPAR-γ
the overexpression of antiapoptotic proteins and the signaling pathway, upregulating PTEN expression and
underexpression of proapoptotic proteins. These changes downregulating COX-2 expression to promote cancer
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can lead to resistance to chemotherapy, a commonly used cell growth. Fenofibrate, an agonist of PPAR-α, hinders
cancer treatment method. Several PPAR agonists have cell proliferation and induces apoptosis in Ishikawa
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demonstrated antiproliferative and apoptosis-inducing endometrial carcinoma cells. These effects are magnified
effects when used in combination with chemotherapeutic by retinoic acid, an agonist of the retinoid X receptor.
agents, and the underlying pathways are illustrated in DNA content analysis indicates that progression through
Figure 2. Treatment with PPAR-γ through the synthetic the G1/S phase of the cell cycle is inhibited. Independent
ligand TGZ and all-trans-retinoic acid significantly component analysis of gene microarray experiments shows
inhibited the growth of MCF7 tumors, which was a reduction in the expression of cyclin D1 (CCND1) and
correlated with the downregulation of Bcl-2 and resulted related changes in cell cycle gene expression. 71
in significant apoptosis and fibrosis in these tumors. 67 A PPAR-γ agonist, TGZ, in combination with cisplatin,
In certain cancer cell lines, ranpirnase and rosiglitazone inhibited EHMES-10 cell growth through cell cycle arrest
work synergistically to reduce cell viability and accelerate due to the overexpression of p21 waf1/cip1 and apoptosis. This
cell death. For malignancies with elevated PI3K-dependent synergism may provide therapeutic benefits for patients
Fra-1 expression or survivin, the innovative combination with malignant pleural mesothelioma. The combination
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Figure 2. Effect of peroxisome proliferator-activated receptor (PPAR) agonists as an adjuvant on the proliferation and apoptosis of cancer cells. PPAR
ligand along with paclitaxel, cisplatin, ranpirnase, all-trans-retinoic acid, and 5-fluorouracil exert more effects than cancer therapy alone. The effects of
PPAR agonists were due to the decreased expression of Bcl2, survivin, PI3K, AKT, MDM2, and p53 and the increased expression of Bax. This finally leads
to the activation of apoptotic pathways in cancer cells.

Volume 3 Issue 4 (2024) 5 doi: 10.36922/td.4003