PART 1
Quercetin, a plant-derived flavonoid found in fruits, vegetables and tea, has been known to possess bioactive properties such as anti-oxidant, anti-inflammatory and anti-cancer. In this study, anti-cancer effect of quercetin and its underlying mechanisms in triple-negative breast cancer c...
PART 1
Quercetin, a plant-derived flavonoid found in fruits, vegetables and tea, has been known to possess bioactive properties such as anti-oxidant, anti-inflammatory and anti-cancer. In this study, anti-cancer effect of quercetin and its underlying mechanisms in triple-negative breast cancer cells was investigated. MTT assay showed that quercetin reduced breast cancer cell viability in a time and dose dependent manner. For this, quercetin not only increased cell apoptosis but also inhibited cell cycle progression. Moreover, quercetin increased FasL mRNA expression and p51, p21 and GADD45 signaling activities. It was observed that quercetin induced protein level, transcriptional activity of Foxo3a. Knockdown of Foxo3a caused significant reduction in the effect of quercetin on cell apoptosis and cell cycle arrest. In addition, treatment of JNK inhibitor (SP 600125) abolished quercetin-stimulated Foxo3a activity, suggesting JNK as a possible upstream signaling in regulation of Foxo3a activity. Knockdown of Foxo3a and inhibition of JNK activity reduced the signaling activities of p53, p21 and GADD45, triggered by quercetin. This study, thus, suggests that quercetin induces apoptosis and cell cycle arrest via modification of Foxo3a signaling in triple-negative breast cancer cells.
PART 2
Lysophosphatidic acid, LPA has been known as a popular growth factor derived from platelet. LPA induction of breast cancer cell proliferation, motility and migration has been investigated in many previous studies. Moreover, LPA was able to induce angiogenesis leading to metastasis outset. Recently, several evidences suggested that LPA has an important role in bone metastasis; however, its mechanism is still not fully understood. Besides, IL-8 and IL-11 has been known as cytokines mostly implied in breast cancer metastasis to bone. LPA induces IL-8 expression and secretion in several breast cancer cells. Therefore, here the effect of LPA on breast cancer progression and regulation of these cytokines in LPA-treated breast cancer cells was investigated. Real-time PCR revealed that IL-8 and IL-11 were upregulated in LPA-treated MDA-MB-231 cells. It was observed that IL-8 was induced in both MDA-MB-231 and MDA-MB-468 (both cell lines express LPA2), however, IL-11 was induced in only MDA-MB-231 (the only cell line expresses LPA1), suggesting different LPARs may be involved in regulation of these cytokines. It was shown that IL-8 but not IL-11 expression was inhibited by PI3K, NF-kB, ROCK and PKC inhibitors (Go6976). However, IL-11 expression was inhibited by specific PKC subtype inhibitors GF109203X and rottlerin, suggesting PKCδ may be responsible for IL-11 expression. And IL-8 expression that was inhibited by Go6976 but not GF109203X, suggesting for possible involvement of PKCμ in regulation of IL-8. Moreover, conditioned media from LPA-stimulated breast cancer cells promoted osteoclastogenesis. Taken together, this study suggests LPA may have a role in bone metastasis via regulation of IL-8 and IL-11.
PART 1
Quercetin, a plant-derived flavonoid found in fruits, vegetables and tea, has been known to possess bioactive properties such as anti-oxidant, anti-inflammatory and anti-cancer. In this study, anti-cancer effect of quercetin and its underlying mechanisms in triple-negative breast cancer cells was investigated. MTT assay showed that quercetin reduced breast cancer cell viability in a time and dose dependent manner. For this, quercetin not only increased cell apoptosis but also inhibited cell cycle progression. Moreover, quercetin increased FasL mRNA expression and p51, p21 and GADD45 signaling activities. It was observed that quercetin induced protein level, transcriptional activity of Foxo3a. Knockdown of Foxo3a caused significant reduction in the effect of quercetin on cell apoptosis and cell cycle arrest. In addition, treatment of JNK inhibitor (SP 600125) abolished quercetin-stimulated Foxo3a activity, suggesting JNK as a possible upstream signaling in regulation of Foxo3a activity. Knockdown of Foxo3a and inhibition of JNK activity reduced the signaling activities of p53, p21 and GADD45, triggered by quercetin. This study, thus, suggests that quercetin induces apoptosis and cell cycle arrest via modification of Foxo3a signaling in triple-negative breast cancer cells.
PART 2
Lysophosphatidic acid, LPA has been known as a popular growth factor derived from platelet. LPA induction of breast cancer cell proliferation, motility and migration has been investigated in many previous studies. Moreover, LPA was able to induce angiogenesis leading to metastasis outset. Recently, several evidences suggested that LPA has an important role in bone metastasis; however, its mechanism is still not fully understood. Besides, IL-8 and IL-11 has been known as cytokines mostly implied in breast cancer metastasis to bone. LPA induces IL-8 expression and secretion in several breast cancer cells. Therefore, here the effect of LPA on breast cancer progression and regulation of these cytokines in LPA-treated breast cancer cells was investigated. Real-time PCR revealed that IL-8 and IL-11 were upregulated in LPA-treated MDA-MB-231 cells. It was observed that IL-8 was induced in both MDA-MB-231 and MDA-MB-468 (both cell lines express LPA2), however, IL-11 was induced in only MDA-MB-231 (the only cell line expresses LPA1), suggesting different LPARs may be involved in regulation of these cytokines. It was shown that IL-8 but not IL-11 expression was inhibited by PI3K, NF-kB, ROCK and PKC inhibitors (Go6976). However, IL-11 expression was inhibited by specific PKC subtype inhibitors GF109203X and rottlerin, suggesting PKCδ may be responsible for IL-11 expression. And IL-8 expression that was inhibited by Go6976 but not GF109203X, suggesting for possible involvement of PKCμ in regulation of IL-8. Moreover, conditioned media from LPA-stimulated breast cancer cells promoted osteoclastogenesis. Taken together, this study suggests LPA may have a role in bone metastasis via regulation of IL-8 and IL-11.
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