Inhibition of growth of cervical cancer cells using a dominant negative estrogen receptor gene

Au, William W.; Abdou-Salama, Salama; Al-Hendy, Ayman

doi:10.1016/j.ygyno.2006.10.015

Cited by 21 publications

(17 citation statements)

References 32 publications

(32 reference statements)

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“…Cervical cancer is the second leading cause of cancer morbidity and mortality for women around the world, especially in many developing countries [1] . The aberrancy of signaling pathways is critical in the pathogenesis and progression of cancers.…”

Section: Introductionmentioning

confidence: 99%

AICAR inhibits proliferation and induced S-phase arrest, and promotes apoptosis in CaSki cells

Guan

Qin

et al. 2007

Acta Pharmacologica Sinica

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Aim: The aim of the present study was to determine the effect of 5‐aminoimidazole‐4‐carboxamide‐ribonucleoside (AICAR) on proliferation, cell cycle, and apoptosis in the human epithelial cervical cancer cell line CaSki cells. Methods: Cell count and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay were used to determine cell proliferation and viability. Hoechst 33258 staining was conducted to distinguish the apoptotic cells. Cell cycle and Annexin‐V/propidium iodide staining were analyzed by fluorescence‐activated cell sorting (FACS). A Western blot assay was used to evaluate the expression of AKT (also known as protein kinase B), mammalian target of rapamycin (mTOR), p53, and extracellular signal‐regulated kinase (ERK). Results: AICAR (500 μmol/L) significantly inhibited the proliferation of CaSki cells treated for 24, 48, and 72 h as determined by cell count. The cells at the G1 and G2 phases were dramatically decreased while cells at the S phase were increased in response to AICAR treatment for 24, 48, and 72 h. The MTT assay showed less viable cells and Hoechst fluorescent staining showed more apoptotic cells upon AICAR stimulation. The results of the Annexin‐V staining demonstrated a time‐dependent increase of apoptosis in cells treated with AICAR for 24, 36, and 48 h. Furthermore, AICAR activated caspase‐3 in a time‐dependent manner. It was also found that AICAR inhibited the phosphory‐lation of AKT and mTOR, which are important kinases regulating cell growth and survival. AICAR stimulation obviously increased the expression of the tumor suppressor p53 and the phosphorylation of ERK. Conclusion: AICAR inhibited proliferation and induced S phase arrest and promoted apoptosis in CaSki cells, which might be mediated by the downregulation of the AKT/mTOR pathway and the upregulation of the p53/ERK pathway.

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Section: Introductionmentioning

confidence: 99%

AICAR inhibits proliferation and induced S-phase arrest, and promotes apoptosis in CaSki cells

Guan

Qin

et al. 2007

Acta Pharmacologica Sinica

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“…[83] Estrogen is responsible for the onset, persistence, and malignant transformation of cervical cells [84] by stimulating oncogenic expression of HPV's E6 and E7 proteins promoting viral proliferation [17] and driving cells through the cell cycle. [85] Additionally, ROS activates HPV [16] and its E6 protein can in turn cause production of more ROS and DNA damage.…”

Section: Discussionmentioning

confidence: 99%

“…[13] In contrast, UVB produces vitamin D 3 in the skin [14] that also circulates systemically and may counter the effects of the inflammatory cytokines and possibly even decrease the risk for getting some cancers. [15] UVA radiation creates ROS that can further contribute toward carcinogenesis by activating HPV [16] and combined with estrogen cause increased expression of HPV's oncogenic proteins E6 and E7 [17] that immortalize cells by inactivating p53 and pRB, respectively. [18] ROS synergistically increases the risk for getting cancer when combined with estrogen, as shown in a hamster kidney cancer model.…”

Section: Introductionmentioning

confidence: 99%

All sites but skin cancer incidences analyzed worldwide by sex, age, and skin type over time (1955-2007), advancing age, and UVB dose reveals important carcinogenic drivers

Godar

Gurov²,

Merrill

2017

JER

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Because we observed increasing incidences over time, advancing age, higher estrogen levels, decreasing UVB (290-315 nm) doses, or lower vitamin D3, and Human Papillomavirus hiding in immune-privileged sites of hair follicles play roles in melanoma, we wondered if the majority of cancers might have similar carcinogenic drivers. To investigate this possibility, we performed worldwide analysis of all sites but skin cancer over time , advancing age, and UVB doses for males and females with all skin types and ages (0-85+) and in five age groups using IARC data. To investigate Human Papillomavirus's role, we analyzed the incidences of breast, prostate, and colon cancers in a developed country with European ancestry (New Zealand) having high amounts of androgenic hair and a developing country with Asian ancestry (India) having low amounts of androgenic hair. To potentially add epidemiology to the already established role of estrogen in cancer, we analyzed males and females in various countries around the world using the incidence of breast cancer (> 70 yr.) as an established indicator of estrogen levels. The analysis reveals cancer incidences are steadily increasing over time in developed but not developing countries regardless of skin type. Only US white, but not black, breast, prostate, and colon cancer incidences in the oldest age group significantly decreased with increasing UVB dose suggesting a role for vitamin D3. The data suggests the carcinogenic drivers in many cancers are estrogen, increasing age (or reactive oxygen species), decreasing vitamin D3 levels, and persistence of Human Papillomavirus infection in immune-privileged sites.

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“…[41] The mechanism involves estrogen stimulating oncogene expression of HPV E6 and E7 proteins and promoting viral proliferation. [42] ROS synergizes with estrogen to cause cancer, [43] it activates HPV, [44] and HPV's E6 protein can in turn cause production of ROS and DNA damage. [45] The estrogen receptor alpha also plays an important role in this transformation process [40,46] and low levels of vitamin D 3 help promote cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Cutaneous malignant melanoma incidences analyzed worldwide by skin type over advancing age of males and females: Evidence estrogen and androgenic hair are risk factors

Godar¹,

Subramanian

Merrill

2016

JER

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We previously analyzed cutaneous malignant melanoma (CMM) incidences worldwide by sex, age, and Fitzpatrick skin type over time and found only European-ancestry populations have exponential increasing incidences and about a 2-log increase in the risk between the youngest age groups (0-14 and 15-29 yr). We proposed the increasing incidence over time may be from the spread of Human Papilloma Virus (HPV) found in CMM biopsies, and that the 2-log incidence increase between the youngest age groups might be from developing androgenic hair. The increasing incidence with age may be from white hairs transmitting UV radiation to follicular melanocytes. Here we analyzed CMM incidences over the advancing age of males and females of every skin type (I-VI) worldwide. We found only European-ancestry females have a linear increase in their CMM risk while males of all races have a power function increase in their risk with advancing age. We propose the gradual loss of HPV-infected androgenic follicles with advancing age of only European-ancestry females during and after menopause significantly reduces their CMM risk compared to all males who do not have significant estrogen loss and consequent loss of androgenic hair with advancing age. All other races have females with significantly lower amounts of androgenic body hair so that its loss with advancing age is not significant. These results combined with those in the literature and our previous findings showing CMM has been increasing over time, suggests estrogen synergizes HPV infection of androgenic follicular melanocytes significantly increasing the risk for getting CMM.

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Inhibition of growth of cervical cancer cells using a dominant negative estrogen receptor gene

Cited by 21 publications

References 32 publications

AICAR inhibits proliferation and induced S-phase arrest, and promotes apoptosis in CaSki cells

AICAR inhibits proliferation and induced S-phase arrest, and promotes apoptosis in CaSki cells

All sites but skin cancer incidences analyzed worldwide by sex, age, and skin type over time (1955-2007), advancing age, and UVB dose reveals important carcinogenic drivers

Cutaneous malignant melanoma incidences analyzed worldwide by skin type over advancing age of males and females: Evidence estrogen and androgenic hair are risk factors

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